EFFECT OF CO2 ON SUSCEPTIBILITIES OF ANAEROBES TO ERYTHROMYCIN, AZITHROMYCIN, CLARITHROMYCIN, AND ROXITHROMYCIN

The Oxyrase agar dilution method (Oxyrase, Inc., Mansfield, Ohio), whi ch provides an anaerobic environment without added CO2, was compared w ith the reference agar dilution method recommended by the National Com mittee for Clinical Laboratory Standards (anaerobic chamber with 10% C O2) to test the susceptibilities of 302 gram-negative and gram-positiv e anaerobes to erythromycin, azithromycin, clarithromycin, and roxithr omycin. For erythromycin, the overall MIC for 50% of isolates tested ( MIC(50)) was 0.5 mu g/ml and the MIC(90) was 8.0 mu g/ml by the Oxyras e method, whereas they were 4.0 and 64.0 mu g/ml, respectively, under standard anaerobic conditions with CO2. At a breakpoint of 4.0 mu g/ml , 88% of strains were susceptible to erythromycin by the Oxyrase metho d, whereas 63% were susceptible in the chamber. The corresponding MIC( 50)s and MIC(90)s of azithromycin, clarithromycin, and roxithromycin b y the Oxyrase method were 0.5 and 8.0, 0.25 and 4.0, and 0.5 and 16.0 mu g/ml, respectively, whereas in the chamber they were 4.0 and >64.0, 2.0 and 64.0, and 2.0 and 64.0 mu g/ml, respectively. At a breakpoint of 8.0 mu g/ml for these three drugs, 89, 92, and 85% of the isolates , respectively, were susceptible by the Oxyrase method, whereas 67%, 7 2, and 68% of the isolates, respectively, were susceptible in the cham ber. Most strains resistant to all four compounds by both methods were Bacteroides distasonis, Fusobacterium mortiferum, Fusobacterium variu m and non-Clostridium perfringens Clostridium species. Results of the study may lead to a reappraisal of the role played by macrolides and a zalides in the treatment of anaerobic infections.